Xenoport, Inc.

Onyx Therapeutics, Inc.

Amgen Inc.

Arbor Pharmaceuticals, LLC

Ge Peng

Mark A Gallop

Thu Phan

Fenmei Yao

Maria J Ludwikow

Pasit Phiasivongsa

Gary W Luehr

Shabbir T Anik

Stephen P Raillard

Suresh Kumar Manthati

Xuedong Dai

Randall A Scheuerman

Seema Rani Bhat

Kolbot By

Kenneth C Cundy

Feng Xu

Irina Dotsenko

Thomas F Woiwode

Usha Dilip

Dante Romanini

David Juergen Wustrow

Maria Ludwikow

The present invention provides a method of treating multiple myeloma using polymeric pegylated carfilzomib compounds, and pharmaceutically acceptable salts thereof, of Formula I wherein R, R, linker, PEG, n and o are as defined herein.

Pegylated carfilzomib compounds

This disclosure features compounds that are useful as pro-drugs of epoxy ketone protease inhibitors.

Prodrugs of peptide epoxy ketone protease inhibitors

The present invention provides polymeric pegylated carfilzomib compounds, and pharmaceutically acceptable salts thereof, of Formula I wherein R, R, linker, PEG, n and o are as defined herein. The invention also provides methods of making and using these compounds to treat cancer, and particularly to treat hematological malignancies including multiple myeloma.

The disclosures herein relate generally to acyloxyalkyl carbamate prodrugs of (&#xb1;)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, pharmaceutical compositions thereof, methods of making prodrugs of (&#xb1;)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, methods of using prodrugs of (&#xb1;)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof, and pharmaceutical compositions thereof for treating or preventing common diseases and/or disorders such as spasticity and/or acid reflux disease. The disclosures herein also relate to acyloxyalkyl carbamate prodrugs of (&#xb1;)-4-amino-3-(4-chlorophenyl)butanoic acid and analogs thereof which are suitable for oral administration and to sustained release oral dosage forms thereof.

Acyloxyalkyl carbamate prodrugs, methods of synthesis and use

Methods for synthesis of 1-(acyloxy)-alkyl carbamates, particularly, the synthesis of 1-(acyloxy)-alkyl carbamate prodrugs of primary or secondary amine-containing drugs are described. Also described are methods for synthesis of 1-(acyloxy)-alkyl N-hydroxysuccinimidyl carbonates which are useful intermediates in the synthesis of 1-(acyloxy)-alkyl carbamates are also described.

Synthesis of acyloxyalkyl carbamate prodrugs and intermediates thereof

Provided herein are compounds of formula (I): which are pro-drugs of epoxy ketone protease inhibitors. The compounds disclosed herein include one or more moieties that (i) confer enhanced solubility, permeability, pharmacokinetics, and/or pharmacodynamics properties to epoxy ketone protease inhibitors, and (ii) can be released in vivo. Also provided herein are pharmaceutical compositions of the compounds of formula (I), and methods of using the compounds of formula (I) to treat diseases and conditions.

Gamma-amino-butyric acid derivatives that are GABAreceptor ligands, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives and pharmaceutical compositions thereof for treating diseases are disclosed.

[object Object]

Methods of enzymatically resolving acyloxyalkyl thiocarbonates useful in the synthesis of acyloxyalkyl carbamate prodrugs are disclosed.

Enantiomerically resolving acyloxyalkyl thiocarbonates used in synthesizing acyloxyalkyl carbamate prodrugs

The present invention provides gemcitabine prodrugs, methods of making gemcitabine prodrugs, pharmaceutical compositions of gemcitabine prodrugs and methods of using gemcitabine prodrugs and pharmaceutical compositions of using gemcitabine prodrugs to treat or prevent diseases or disorders such as cancer or viral infections.

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Mountain View, CA, United States of America

Ge Peng